Realized evolvability: quantifying phenotypic evolution in a Drosophila clade

Understanding the evolutionary potential of morphological evolution is still a major problem in evolutionary biology. In this study, we tried to quantify the amount of variation of different traits among species of a Drosophila clade reared under standard conditions. Nineteen different traits have been measured on nine species of the same clade, the Neotropical saltans group of Drosophila. Measured traits can be distributed into five categories: size‐traits (wing and thorax), shape indices (ratios among the size traits), number of sternopleural bristles on the thorax, number of abdominal bristles on successive sternites, and dorsal pigmentation of abdomen. All species are of medium size with a generally dark pigmentation. A remarkable feature is the presence of numerous bristles on the 6th sternite of the males, while this segment is bare in other Drosophila species. A multivariate analysis revealed that it was possible to discriminate all the investigated species by using the complete set of measured traits. For each trait, phenotypic variability was investigated at the within‐ and between‐species levels. As a rule, the interspecific coefficient of variation (CV) was much greater than the within species CV, and it is proposed to call it realized evolvability. All possible correlations were calculated between traits across species, providing many unexpected results. Size traits were highly correlated among them, but not correlated with shape indices. Abdominal traits (bristles and pigmentation) were correlated, but often in opposite directions, with thoracic shape indices. Tergite pigmentation was negatively correlated with bristle number on sternite. For the moment, most of the correlations cannot be explained by developmental processes or parallel selective pressures. Nonetheless, mapping the evolution of the two characters on a molecular phylogeny of the studied species revealed two opposite phylogenetic trends for abdominal pigmentation and setation, respectively. Our data suggest a need for similar studies in other well‐defined Drosophila clades.     

Is a rise in intracellular concentration of free calcium necessary or sufficient for stimulated cytoskeletal-associated actin?

The addition of the calcium ionophore A23187 to rabbit neutrophils increases the amount of actin associated with the cytoskeleton regardless of the presence or absence of calcium in the incubation medium. In the presence of extracellular calcium, the effect of A23187 is biphasic with respect to concentration. The action of the ionophore is rapid, transient, and is inhibited by pertussis toxin, hyperosmolarity, and quinacrine. On the other hand, the addition of pertussis toxin or hyperosmolarity has small if any, effect on the rise in intracellular calcium produced by A23187. While quinacrine does not affect the fMet-Leu-Phe-induced increase in cytoskeletal actin and the polyphosphoinositide turnover, its addition inhibits completely the stimulated increase in Ca-influx produced by the same stimulus. The results presented here suggest that a rise in the intracellular concentration of free calcium is neither necessary nor sufficient for the stimulated increase in cytoskeletal-associated actin. A possible relationship between the lipid remodeling stimulated by chemoattractants and the increased cytoskeletal actin is discussed.     

StructureActivity Relationships of Antimicrobial Gallic Acid Derivatives from Pomegranate and Acacia Fruit Extracts against Potato Bacterial Wilt Pathogen

Bacterial wilts of potato, tomato, pepper, and or eggplant caused by Ralstonia solanacearum are among the most serious plant diseases worldwide. In this study, the issue of developing bactericidal agents from natural sources against R. solanacearum derived from plant extracts was addressed. Extracts prepared from 25 plant species with antiseptic relevance in Egyptian folk medicine were screened for their antimicrobial properties against the potato pathogen R. solancearum by using the disc‐zone inhibition assay and microtitre plate dilution method. Plants exhibiting notable antimicrobial activities against the tested pathogen include extracts from Acacia arabica and Punica granatum. Bioactivity‐guided fractionation of A. arabica and P. granatum resulted in the isolation of bioactive compounds 3,5‐dihydroxy‐4‐methoxybenzoic acid and gallic acid, in addition to epicatechin. All isolates displayed significant antimicrobial activities against R. solanacearum (MIC values 0.5–9 mg/ml), with 3,5‐dihydroxy‐4‐methoxybenzoic acid being the most effective one with a MIC value of 0.47 mg/ml. We further performed a structure–activity relationship (SAR) study for the inhibition of R. solanacearum growth by ten natural, structurally related benzoic acids.     

Chemotactic factor causes rapid decreases in phosphatidylinositol,4,5-bisphosphate and phosphatidylinositol 4-monophosphate in rabbit neutrophils

Stimulation of rabbit neutrophils prelabeled with 32P by the synthetic chemotactic peptide f-Met-Leu-Phe induces a rapid decrease in the radioactivity in both phosphatidylinositol, 4,5 bis phosphate and phosphatidylinositol 4-monophosphate. The mean +/- standard error of the mean values of the maximum decrease in phosphatidylinositol, 4,5 bis phosphate occurred at 10 seconds following stimulation and is equal to 19 +/- 3% of the control value. The corresponding value for phosphatidylinositol 4-monophosphate occurred at 60 seconds following stimulation and is equal to 37 +/- 7% of the control value. On the other hand, the radioactivity in phosphatidic acid and lysophospholipids increased continuously with time following stimulation. The relationship of these changes to calcium release and neutrophil activation is discussed.     

Role of mutation Y6F on the binding properties of Schistosoma japonicum glutathione S-transferase

The role of the hydroxyl group of tyrosine 6 in the binding of Schistosoma japonicum glutathione S-transferase has been investigated by isothermal titration calorimetry (ITC). A site-specific replacement of this residue with phenylalanine produces the Y6F mutant, which shows negative cooperativity for the binding of reduced glutathione (GSH). Calorimetric measurements indicated that the binding of GSH to Y6F dimer is enthalpically driven over the temperature range investigated. A concomitant net uptake of protons upon binding of GSH to Y6F mutant was detected carrying out calorimetric experiments in various buffer systems with different heats of ionization. The entropy change is favorable at temperatures below 26 °C for the first site, being entropically favorable at all temperatures studied for the second site. The enthalpy change of binding is strongly temperature-dependent, arising from a large negative ΔC°_p1=−3.45±0.62 kJ K⁻¹ mol⁻¹ for the first site, whereas a small ΔC°_p2=−0.33±0.05 kJ K⁻¹ mol⁻¹ for the second site was obtained. This large heat capacity change is indicative of conformational changes during the binding of substrate.     

Ten years primary succession on a newly created landfill at a lagoon of the Mediterranean Sea (Lake Burullus RAMSAR site)

This study was carried out on the transported bed soil dredged from the outlet of Lake Burullus to the Mediterranean Sea and deposited nearby, forming by this way new land that underwent a primary plant succession. The multi-methodological approach comprised floristic inventories, vegetation sampling and soil composition analyses of the study site in order to detect the crucial parameters controlling the plant resettlement on recently deposited soil as related to time, local micro-topography and substrate characteristics. Floristic composition was assessed for the first 10 years of primary succession (2001–2010) on 18 stands of the area, distributed on basement, slope stands and plateau of the landfill, respectively. Vegetation surveys were the basis of multivariate analyses of the vegetation and soil data using TWINSPAN, DCA and CCA. Relationships between the edaphic gradients, floristic composition and species diversity were assessed.     

Haematopoietic stem cell gene therapy to treat autoimmune disease

Autoimmune diseases affect approximately 6% of the population and are characterised by a pathogenic immune response that targets self-antigens. Well known diseases of this nature include type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Treatment is often restricted to replacement therapy or immunosuppressive regimes and to date there are no cures. The strategy of utilising autologous or allogeneic haematopoietic stem cell transplantation to treat autoimmunity and induce immunological tolerance has been trailed with various levels of success. A major issue is disease relapse as the autoimmune response is reinitiated. Cells of the immune system originate from bone marrow and have a central role in the induction of immunological tolerance. The ability to isolate and genetically manipulate bone marrow haematopoietic stem cells therefore makes these cells a suitable vehicle for driving ectopic expression of defined autoantigens and induction of immunological tolerance.     

The inhibition of neutrophil granule enzyme secretion and chemotaxis by pertussis toxin

Pertussis toxin treatment of rabbit peritoneal neutrophils causes a concentration-dependent inhibition of granule enzyme secretion induced by formylmethionyl-leucyl-phenylalanine, C5a, and leukotriene B4. It also inhibits chemotaxis induced by formylmethionyl-leucyl-phenylalanine. The same toxin treatment, however, has no effect on granule enzyme secretion induced by the calcium ionophore A23187 or phorbol 12-myristate 13-acetate. Moreover, pertussis toxin treatment does not affect either the number or affinity of the formylpeptide receptors on the neutrophil nor does it have any effect on the unstimulated levels of cyclic AMP (cAMP) or the transient rise in cAMP induced by chemotactic factor stimulation in these cells. We hypothesize that pertussis toxin, as in other cells, interacts with a GTP binding regulatory protein identical with or analogous to either Ni or transducin which mediates the receptor-induced inhibition or activation of a target protein or proteins required in neutrophil activation. The nature of the target protein is unknown, but it is not the catalytic unit of adenylate cyclase. The target protein acts after binding of chemotactic factor to its receptor in the sequence that leads to the receptor-induced rise in intracellular Ca2+. It does not affect the responses elicited by the direct introduction of calcium into the cells or the activity of protein kinase C.     

Multivariate frailty models for two types of recurrent events with a dependent terminal event: Application to breast cancer data

Individuals may experience more than one type of recurrent event and a terminal event during the life course of a disease. Follow‐up may be interrupted for several reasons, including the end of a study, or patients lost to follow‐up, which are noninformative censoring events. Death could also stop the follow‐up, hence, it is considered as a dependent terminal event. We propose a multivariate frailty model that jointly analyzes two types of recurrent events with a dependent terminal event. Two estimation methods are proposed: a semiparametrical approach using penalized likelihood estimation where baseline hazard functions are approximated by M‐splines, and another one with piecewise constant baseline hazard functions. Finally, we derived martingale residuals to check the goodness‐of‐fit. We illustrate our proposals with a real dataset on breast cancer. The main objective was to model the dependency between the two types of recurrent events (locoregional and metastatic) and the terminal event (death) after a breast cancer.